Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells

TL;DR

This study explores how L-histidine affects bovine mammary cells under high fat conditions, identifying a key metabolite that could help prevent ketosis in cows.

Contribution

The study identifies 1-Linoleoylglycerophosphocholine as a potential key mediator in the interaction between NEFA and L-histidine in bovine cells.

Findings

NEFA treatment altered 893 and 160 metabolites in positive and negative models, respectively.

L-histidine treatment altered 61 and 34 metabolites in positive and negative models, respectively.

1-Linoleoylglycerophosphocholine was regulated oppositely by NEFA and L-histidine.

Abstract

Ketosis in cows occurs when excessive ketone bodies are produced by the liver, typically due to energy deficits from reduced feed intake or specific dietary conditions. Scientists have noticed that cows with ketosis have lower amounts of a substance named L-histidine. This sparked curiosity about how L-histidine might help cows with this problem. To understand this better, researchers looked at changes in cow mammary cells caused by the fat and whether L-histidine could help. They found many changes in the cell’s substances, some increasing and some decreasing, showing that the cells were trying to respond to the fat. Interestingly, when L-histidine was added, it seemed to help by changing some of these substances, suggesting it might protect the cells. One particular substance seemed to play a big role and was affected by both the fat and L-histidine in different ways. This research helps us understand the complicated ways cow cells react to excess fat and suggests that L-histidine could be a helpful tool in keeping cows healthy, which is valuable for farmers and the dairy industry.

Non-esterified fatty acids (NEFAs) are pivotal in energy metabolism, yet high concentrations can lead to ketosis, a common metabolic disorder in cattle. Our laboratory observed lower levels of L-histidine in cattle suffering from ketosis, indicating a potential interaction between L-histidine and NEFA metabolism. This relationship prompted us to investigate the metabolomic alterations in bovine mammary epithelial cells (BMECs) induced by elevated NEFA levels and to explore L-histidine’s potential mitigating effects. Our untargeted metabolomic analysis revealed 893 and 160 metabolite changes in positive and negative models, respectively, with VIP scores greater than 1 and p-values below 0.05. Notable metabolites like 9,10-epoxy-12-octadecenoic acid were upregulated, while 9-Ethylguanine was downregulated. A pathway analysis suggested disruptions in fatty acid and steroid biosynthesis pathways. Furthermore, L-histidine treatment altered 61 metabolites in the positive model and 34 in the negative model, with implications for similar pathways affected by NEFA. Overlaying differential metabolites from both conditions uncovered a potential key mediator, 1-Linoleoylglycerophosphocholine, which was regulated in opposite directions by NEFA and L-histidine. Our study uncovered that both NEFA L- and histidine metabolomics analyses pinpoint similar lipid biosynthesis pathways, with 1-Linoleoylglycerophosphocholine emerging as a potential key metabolite mediating their interaction, a discovery that may offer insights for therapeutic strategies in metabolic diseases.

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